1. Field of Invention
The present invention relates to novel aromatic oxazepinones, thiazepinones and diazepinones and sulfur analogs thereof and is particularly concerned with aromatic 1,4-oxazepinones, thiazepinones, diazepinones and thiones of all, which have the aromatic component fused into the oxazepine, thiazepine or diazepine component, each component thereby having two commonly shared carbon atoms and the oxazepine, thiazepine or diazepine ring having an oxo (or thioxo) function on the carbon atom adjacent to one of the shared carbon atoms and a short chain aminoalkyl, alkylaminoalkyl or heterocyclicaminoalkyl radical attached to the carbon atom two positions away from the other shared carbon atom, the compounds having antihistaminic and anti-allergy utility, and a novel process and novel intermediates for the preparation thereof.
2. Information Disclosure Statement.
3-Aryl-1,4-benzoxazepin-5(4H)-ones substituted on the oxazepine nitrogen by an aminoalkyl radical have been disclosed by Schenker, K. in Swiss Patent 505.850 (C.A. 75 98600s).
Conversion of flavanones into benzoxazepinones substituted in the 2-position by a phenyl radical has been disclosed by Levai, A. and Bognar, R., Top. Flavanoid Chem. Biochem. Proc. Hung. Bioflavonoid Symp. 4th Ed. 1973 (Pub. 1975) 119-23 (C.A. 85, 79098n). Thione derivatives were obtained by treating with phosphorus pentasulfide.
Certain chemical intermediates, the 1-substituted-3-substituted phenoxypyrrolidines illustrated by
1-methyl-3-(2-carbamoylphenoxy)pyrrolidine, PA0 1-benzyl-3-(2-carbamoylphenoxy)pyrrolidine, and PA0 1-methyl-3-(2-carboxyphenoxy)pyrrolidine, PA0 (a) thionyl halides PA0 (b) triphenylphosphine and a carbon tetrahalide PA0 (c) phosphorus pentahalides PA0 (d) phosphorus trihalides, PA0 (e) triphenylphosphine dihalide, and PA0 (f) oxalyl chloride. PA0 (a) formaldehyde and formic acid to give a tertiary dimethylamine, PA0 (b) a dihalide or alkenedihalide to give a heterocyclic amine, PA0 (c) a dialdehyde and sodium cyanoborohydride to give a heterocyclic amine, PA0 (d) equal molar amounts of aldehyde or ketone, sodium cyanoborohydride with large excess of above primary amine to give a secondary amine, PA0 (e) equal molar amounts of the primary amine and sodium cyanoborohydride with at least two equivalents of aldehyde or ketone, PA0 (f) in sequence: trifluoroacetyl chloride, alkyl or phenyl-alkyl halide, potassium hydride and potassium hydroxide to give a secondary amine, PA0 (R)-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazep ine-5(4H)-thione PA0 2-[(1-cyclohexyl-3-pyrrolidinyl)oxy]benzoic acid, PA0 2-[(1-ethyl-3-pyrrolidinyl)oxy]benzoic acid, PA0 2-[(1-isopropyl-3-pyrrolidinyl)oxy]benzoic acid, PA0 2-[[(1-(4-chlorobenzyl)-3-pyrrolidinyl]oxy]benzoic acid, PA0 2-[[1-(4-methylbenzyl)-3-pyrrolidinyl]oxy]benzoic acid, PA0 2-[[1-(3,5-dimethoxybenzyl)-3-pyrrolidinyl]oxy]benzoic acid, PA0 2-[[1-(trifluoromethylbenzyl)-3-pyrrolidinyl]oxy]benzoic acid, and PA0 2-[[1-(4-nitrobenzyl)-3-pyrrolidinyl]oxy]benzoic acid, and PA0 (a) 2-(2-chloroethyl)-4-cyclohexyl-2,3-dihydro-1,4-benzoxazepin-5(4H)-one, PA0 (b) 2-(2-chloroethyl)-2,3-dihydro-4-ethyl-1,4-benzoxazepin-5(4H)-one, PA0 (c) 2-(2-chloroethyl)-2,3-dihydro-4-isopropyl-1,4-benzoxazepin-5(4H)-one, PA0 (d) 2-(2-chloroethyl)-4-(4-chlorobenzyl)-2,3-dihydro-1,4-benzoxazepin-5(4H)-on e, PA0 (e) 2-(2-chloroethyl)-2,3-dihydro-4-(4-methylbenzyl)-1,4-benzoxazepin-5(4H)-on e, PA0 (f) 2-(2-chloroethyl)-2,3-dihydro-4-(3,5-dimethoxybenzyl)-1,4-benzoxazepin-5(4 H)-one, PA0 (g) 2-(2-chloroethyl)-2,3-dihydro-4-(3-trifluoromethylbenzyl)-1,4-benzoxazepin -5(4H)-one, PA0 (h) 2-(2-chloroethyl)-2,3-dihydro-4-(4-nitrobenzyl)-1,4-benzoxazepin-5(4H)-one . PA0 2-[(1-cyclohexyl-3-pyrrolidinyl)oxy]-3-pyridine carboxylate, PA0 2-[(1-ethyl-3-pyrrolidinyl)oxy]-3-pyridine carboxylate, PA0 2-[(1-isopropyl-3-pyrrolidinyl)oxy]-3-pyridine carboxylate, PA0 2-[[1-(4-chlorobenzyl)-3-pyrrolidinyl]oxy]-3-pyridine carboxylate, PA0 2-[[1-(4-methylbenzyl)-3-pyrrolidinyl]oxy]-3-pyridine carboxylate, PA0 2-[[1-(4-methoxybenzyl)-3-pyrrolidinyl]oxy]-3-pyridine carboxylate, PA0 2-[[1-(3-trifluoromethylbenzyl)-3-pyrrolidinyl]oxy]-3-pyridine carboxylate, and PA0 2-[[1-(4-nitrobenzyl)-3-pyrrolidinyl]oxy]-3-pyridine carboxylate, PA0 (a) 2-(2-chloroethyl)-4-cyclohexyl-2,3-dihydro-pyrido[3,2-f][1,4]oxazepin-5(4H )-one hydrochloride, PA0 (b) 2-(2-chloroethyl)-2,3-dihydro-4-ethylpyrido[3,2-f][1,4]-oxazepin-5(4H)one hydrochloride, PA0 (c) 2-(2-chloroethyl)-2,3-dihydro-4-isopropylpyrido[3,2-f][1,4]-oxazepin-5(4H) -one hydrochloride, PA0 (d) 2-(2-chloroethyl)-4-(4-chlorobenzyl)-2,3-dihydropyrido[3,2-f][1,4]-oxazepi n-5(H)-one hydrochloride, PA0 (e) 2-(2-chloroethyl)-2,3-dihydro-4-(4-methylbenzyl)pyrido[3,2-f][1,4]-oxazepi n-5(4H)-one hydrochloride, PA0 (f) 2-(2-chloroethyl)-2,3-dihydro-4-(4-methoxybenzyl)pyrido[3,2-f][1,4]-oxazep in-5(4H)-one hydrochloride, PA0 (g) 2-(2-chloroethyl)-2,3-dihydro-4-(3-trifluoromethylbenzyl)pyrido[3,2-f][1,4 ]-5(4H)-one hydrochloride, and PA0 (h) 2-(2-chloroethyl)-2,3-dihydro-4-(4-nitrobenzyl)pyrido)[3,2-f][1,4]-oxazepi n-5(4H)-one hydrochloride.
in an otherwise novel class are disclosed in U.S. Pat. No. 3,577,415.